The specific aims are to determine: 1) adenosine release and tissue content of strips isolated from muscles of different fiber types; 2) oxidative capacity of isolated muscle strips; 3) adenosine release from vascularly-isolated dog gracilis muscle and the effects on active hyperemia of drugs that block or potentiate adenosine; 4) release of ions from and the effects of infusions of these ions, singly or in combination, on vascular resistance among the muscles. Strips of muscle will be isolated fromcat gracilis (fast-twitch, glycolytic) and soleus (slow-twitch, oxidative) and dog gracilis muscle (fast-twitch, oxidative) and stimulated to contract isometrically. The release of tissue content of adenosine will be measured to determine whether changes occur under conditions associated with active hyperemia or whether hypoxia is necessary, and whether release differs among the muscles. The use of isolated strips will help to avoid the problem of there being different pools of adenosine. In vascularly-isolated dog gracilis muscles stimulated to contract under free-flow conditions, the time course of adenosine release will be correlated with resistance. If adenosine is a mediator of active hyperemia, drugs that block or potentiate the effects of adenosine would be expected to change the vascular response. Interstitial concentrations of K+, NH4+, and H+ will be monitored in contracting, vascularly-isolated muscle preparations, using ion-selective electrodes. The release of Mg++ into venous blood will also be measured. The effects of combinations of these ions on resistance will be assessed by intraarterial infusions. In view of recent evidence that the Na, K-pump and magnesium may be involved in the genesis of hypertension, an understanding of the physiologic role of these ions in regulating vascular resistance seems necessary to further our understanding of how they may be involved in pathophysiologic states.